Goals: I desire an academic career as a geriatric psychiatrist using neuroimaging findings to better understand neuroanatomic correlates of treatment outcomes in late-life depression. As a new faculty member at Duke University, I am continuing preliminary research examining imaging correlates of treatment response, but it is time to expand the scope of this research. To do so I will need further training and experience in 1) neuroimaging and 2) research design and methodology. Training Experience: I will receive close assessment and tutoring by local experts, as well as mentorship by renowned investigators from other institutions. I will be involved in the assessment and treatment of depressed older individuals, and participate in the analysis of data from this study. I will also take courses in research design, biostatistics, and neuroimaging to supplement this experience. Project Background: Geriatric depression is associated with disability and low quality of life. Many individuals do not respond completely to current treatment: one reason for this poor response may be injury to connections between the prefrontal cortex and basal ganglia, areas implicated in lesion models and functional imaging studies. Diffusion tensor imaging (DTI) can detect and quantify this injury. Hypotheses: Depressed subjects will exhibit greater DTI abnormalities than controls. Greater DTI abnormalities will also be associated with poorer response to acute treatment. At one-year follow-up, depressed subjects will exhibit greater progression of DTI abnormalities than controls. Greater DTI deterioration will also be associated with greater relapse of depression. Methods: Subjects will participate in an acute, 12-week treatment course of sertraline. Baseline assessments and DTI will be obtained. After the acute phase study, subjects will progress to a longitudinal, treatment algorithm-based study; they will receive repeat imaging at one year. Image analysis will focus on frontal areas implicated in depression, particularly the orbital frontal cortex and the dorsolateral prefrontal cortex. Imaging results will be compared with outcome variables using both traditional statistical methods and also statistical parametric mapping (SPM). Discussion: These findings will better describe the role of neural connectivity and striatofrontal dysfunction in geriatric depression.